Baseline data from a multicenter, 5-year,prospective cohort study of Japanese age-related macular degeneration: an AMD2000 report

Purpose

To report research participants’ baseline characteristics in the AMD2000 study, a prospective, multicenter, 5-year, observational cohort study of Japanese age-related macular degeneration (AMD). The characteristics were determined using multimodal imaging.

Methods

Patients with AMD were recruited at 18 clinical sites in Japan between April 2006 and March 2009. Each patient underwent a complete ophthalmic examination, including measurement of best-corrected visual acuity (Landolt chart), indirect ophthalmoscopy, slit-lamp biomicroscopy with a contact lens, optical coherence tomography imaging, fundus photography, and fluorescein and indocyanine green angiography.

Results

Four hundred sixty participants (326 men [70.9%]) were included in the study. At enrollment, 131 eyes (28.5%) had hard drusen and 125 eyes (27.2%) had soft drusen in the macular area. A total of 455 eyes (98.9%) were diagnosed as having wet AMD, and 5 eyes (1.1%), as having dry AMD. Of the 455 eyes with wet AMD, 209 eyes (45.4%) had typical AMD, 228 eyes (49.6%) had polypoidal choroidal vasculopathy (PCV), and 18 eyes (3.9%) had retinal angiomatous proliferation. The size of choroidal neovascularization (CNV) was significantly smaller with indocyanine green angiography than with fluorescein angiography (P < 0.001). Poor baseline visual acuity was associated with cystoid macular edema, older age, scar, extrafoveal macular edema, subfoveal CNV, large branching vascular network, and hard exudates.

Conclusion

Japanese patients with AMD are predominantly male, lack drusen, and have a high rate of PCV.

     

Induced immunity by expression of interleukin-2 or GM-CSF gene in murine neuroblastoma cells can generate antitumor response to established tumors.

We examined whether antitumor immunity could be generated by the inoculation of cytokine-producing murine neuroblastoma cells (C1300), and whether the immunity might be effective for the established tumors of wild-type (wt) cells. For that purpose, we transduced low immunogenic C1300 cells with interleukin-2 (IL-2), GM-CSF, or IL-4 genes. A loss of tumorigenicity in syngeneic mice was observed using IL-2- and GM-CSF- but not IL-4-producing C1300 cells, although their in vitro growth rates were not affected by the transduction. The syngeneic mice that had rejected IL-2 or GM-CSF producers did not develop tumors of wt cells inoculated subsequently, but formed tumors of irrelevant syngeneic mammary tumor cells. Accordingly, the inoculation of IL-2 or GM-CSF producers into immunocompetent mice generated tumor-specific acquired immunity. The induced immunity using IL-2 or GM-CSF producers was also effective in eradicating established subcutaneous tumors of wt cells and in reducing the number of preexisting metastatic foci in the liver. These data suggest a potential application of IL-2- or GM-CSF-producing syngeneic tumor cells for the treatment of low immunogenic neuroblastomas.     

Synergistic interactions between footshocks and non-osmotic hypovolemia on vasopressin secretion in rats

The effects of i.p. injected hypertonic NaCl and polyethylene glycol on the magnitude of increase in plasma vasopressin after footshocks were studied in male rats, to determine whether hypovolemia and body fluid osmolality interact with noxious stimuli on vasopressin secretion. Present data have demonstrated that non-osmotic hypovolemia but not body fluid hyperosmolarity interact significantly and synergistically with footshocks to potentiate vasopressin secretion.     

Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearing carboxyl groups and RGD peptide.

A new class of an anionic poly (ethylene glycol) derivative, PEG-Suc, bearing 17.7 pairs of carboxylic acid-side chains was synthesized. PEG-Suc deposited onto the DNA/polyethyleneimine complexes without destroying them even at high dose ratio. Coating of the DNA complexes by PEG-Suc recharged their surface to negative, and effectively protected them from the albumin-induced aggregation. Paired carboxyl groups in the side chains showed higher proton sponge effect. Negatively charged surface would diminish the electrostatic binding of the complexes to the cells, and the transfection efficiency on the cultured cells was not high. RGD peptide side chain as a ligand to malignant cell surfaces was then introduced to compensate the reduced electrical adhesion. RGD-PEG-Suc-coated plasmid/PEI complex brought about more than 3 times higher reporter protein activity on the cultured B16 cells. Those bio-compatible DNA complexes with ligand attained very high gene expression in tumor, lung, and liver after injection into mouse tail vein.     

Effects of cernitin pollen extract (CN-009) on the isolated bladder smooth muscles and the intravesical pressure

Cernitin pollen extract (CN-009), extract from several pollen species, has been used for urinary dysfunction. As its mode of action has not been clarified, we investigated the action of CN-009 on the isolated bladder smooth muscles of rats, guinea pigs and cats and the intravesical pressure in female rats. CN-009 contracted isolated detrusor muscles of rats, guinea pigs and cats in a concentration-dependent manner. In the guinea pig detrusor muscle, the contractile effect of CN-009 was depressed by atropine, diphenhydramine and increased by cimetidine. In the rat detrusor muscle, the CN-009-induced contraction was depressed by atropine. In adult rats (11-23 weeks old) and aged rats (2 years old), CN-009 showed a dose-dependent increase of intravesical pressure to the same extent in spite of the fact that the aged rats had a lower responsiveness to acetylcholine. In adult rats, the CN-009-induced increase of intravesical pressure was reduced completely by atropine and partly reduced by phentolamine and guanethidine. Three weeks consecutive oral administration of CN-009 tended to increase the basal intravesical pressure and tended to elevate the isoproterenol-induced decrease and serotonin-induced increase in the intravesical pressure. These results suggest that CN-009 contracts the detrusor muscle, a process that is mainly mediated by muscarinic receptor activation. The contraction induced by CN-009 of detrusor muscle causes the increase of intravesical pressure.     

Surface marker studies on activated peripheral blood lymphocytes in idiopathic dilated cardiomyopathy

Expression of interleukin 2 (IL-2) receptor on peripheral blood lymphocytes after stimulation with concanavalin A (Con A) or anti-T3 monoclonal antibody was analyzed in patients with dilated cardiomyopathy (DCM) in order to clarify the abnormalities of lymphocyte activation mechanism in DCM. The expression of IL-2 receptor after the stimulation with either Con A or anti-T3 monoclonal antibody was found to be reduced in the patients with DCM when the results were compared with those of controls. A significant correlation was noticed between the expression of IL-2 receptor after Con A stimulation and T4+/T8+ cell ratio, and between the expression of IL-2 receptor after anti-T3 monoclonal antibody stimulation and the left ventricular end-diastolic pressure (LVEDP). The results suggest that there are abnormalities of lymphocyte activation in DCM and that the alteration may be associated with the cause or clinical conditions of DCM.     

Influence of hemoglobin precipitation on erythrocyte metabolism in alpha and beta thalassemia

Certain aspects of the metabolism of centrifuged young and old erythrocytes in hemoglobin H disease have been examined and compared with similar studies of beta thalassemia and normal cells. Glycolysis, hexose monophosphate shunt activity (HMPS), potassium flux, and glutathione (GSH) content were measured. The distributions of hemoglobins H and F, as well as the activities of erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and glutamic oxalacetic transaminase (GOT), were utilized for estimations of the relative ages of the cell samples. The young erythrocytes in hemoglobin H disease differed in several respects from older hemoglobin H cells. They contained more soluble hemoglobin H and GSH and, after splenectomy, fewer inclusions. HMPS activity was subnormal in hemoglobin H young cells and rose to normal activity in old cells. Potassium flux tended to increase in old cells when inclusions were present.Beta thalassemia young cells contained less hemoglobin F and, after splenectomy, more inclusions than old cells. In addition, they had markedly increased glycolysis and HMPS activity. GSH was randomly distributed. Potassium flux was increased in younger cells and particularly increased when inclusions appeared in younger cells after splenectomy.The results are interpreted to indicate that inclusion formation is associated with increased erythrocyte cation permeability in the thalassemia syndromes. This is not related to the level of intracellular GSH.The decreased HMPS activity in young hemoglobin H cells may be due to the presence of the extra thiols of soluble hemoglobin H which can act as a reducing agent. The substitution of hemoglobin H for glutathione in this capacity would then spare the NADPH-requiring glutathione reductase system. As a consequence, HMPS activity would decline. However, in older cells the oxidized hemoglobin H precipitates; these must rely upon GSH and glutathione reductase activity for thiol reduction capacity. Accordingly, HMPS activity increases to normal in the old cell population.     

Anesthesia for extracorporeal shockwave lithotripsy: Teikyo University Hospital experience using the third generation lithotripter

A single-board certified urologist with training and experience in anesthesiology was assigned to treat 502 patients (185 with renal stones, 317 with ureteral stones) using the Dornier Compact Delta lithotripter under general or epidural anesthesia. Data were obtained regarding stone location, stone size, shockwave use, stone-free rate, and complications. In all, 502 stones were treated with the Dornier Compact Delta lithotripter. Among renal stones, 73% were in the renal pelvis. Among ureteral stones, 60% were in the upper, 10% in the middle, and 30% in the lower ureter. Diameters of 61.8% of stones were less than 1 cm. The mean number of shocks was 3,471 at a mean power setting of 5. The stone-free rate for renal stones was 71.5%, while for ureteral stones this reached 99%. The efficiency quotient was calculated as 0.65. One patient with a renal stone developed perinephric hematoma requiring 3 units of transfusion. With a success rate higher than that reported for other lithotripters, the Dornier Compact Delta lithotripter represents a feasible treatment for urolithiasis. We stress that even in the third generation machines the lithotripsy under anesthesia can improve the treatment efficacy.